Center for Genomics, Evolution and Medicine, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia.
Department of Biology, University of Padua, Padua, Italy.
Eur J Hum Genet. 2024 Nov;32(11):1492-1499. doi: 10.1038/s41431-024-01678-9. Epub 2024 Aug 10.
The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.
欧洲的遗传结构主要是由西部狩猎采集者、早期欧洲农民和草原青铜时代祖先成分的混合形成的。这种结构被认为是 GWAS 和后续研究的混杂因素，并且存在纠正这种结构的黄金标准方法。然而，目前尚不清楚这些祖先成分在多大程度上导致了当今欧洲复杂特征的变异。在这项工作中，我们利用英国生物银行来解决这个问题。通过广泛的人口统计学模拟，利用兄弟姐妹的数据，并结合我们从爱沙尼亚生物银行获得的先前结果，我们仔细评估了我们发现的意义和范围。心率、血小板计数、骨密度和许多其他特征与身高和色素沉着特征分层相似，这些特征可能是不同祖先群体之间选择和分化的目标。我们通过使用兄弟姐妹之间的祖先差异来确认我们的结果，证明了报告的祖先-特征关联不是由环境混杂因素驱动的。我们在不同生物库中的结果的一致性进一步支持了这一点，并表明这些源自新石器时代后混合事件的遗传倾向是整个欧洲变异性的来源，也是潜在的混杂因素。
